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Wednesday, May 8, 2013

Click Chemistry for Pyrrole Synthesis

The Pyrrole heterocycle is an important chemical motif, found widely in pharmaceuticals, natural products, agrochemicals and advanced materials. The introduction of new methods or further the work on technical improvements in order to overcome the limitations (such as low efficiency and selectivity) found in pyrrole synthesis is still a pressing experimental challenge.

The concept of “Click Chemistry” is gaining rapidly due to its high efficiency, selectivity, and yield under mild reaction conditions with a wide variety of readily available starting materials. The copper-catalyzed azide–alkyne cycloaddition (CuAAC) has emerged as the premier example of click chemistry and plays a significant role in organic synthesis.

Prof. Aiwen Lei and coworkers, Wuhan University, Hubei, have developed a silver catalyst “click reaction” for the synthesis of pyrrole, by cycloaddition. This system benefits from readily-available starting materials, low catalyst loading (0.1 eq), short reaction times (2 h) and excellent chemo-selectivity. And, works for both internal and alkyl substituted terminal alkynes in the presence of many functional groups. The extremely mild conditions used, makes this reaction synthetically attractive.

This mechanism involves the formation of silver–acetylide complex and silver–isocyanide complex. Subsequently, the cyclo-addition between complexes would afford the key intermediate complex to be followed by protonation and tautomerization of the intermediate complex to form the desired product.

The catalytic synthesis protocol tolerates a large variety of functional groups, which includes methylthio, methylsulfonyl, and ethynyl groups. Moreover, alkyl substituted terminal alkynes were also found to be suitable reaction partners. Interestingly, both Cu(II) and Cu(I) turned out to be ineffective.